The ascending phase of the plasma ethanol curve is associated with an increase in urine flow and renal magnesium loss. On the descending phase, we have found increased fluid intake, decreased urine flow, significant retention of sodium, and decreased magnesium loss. Although single ascending and descending phases have been characterized, there is no information concerning the effects of multiple ascending and descending phases within 24 hrs. One objective of this grant is to determine the effects of multiple dosing schedules on urine flow, urine composition and body fluid compartments, i.e., plasma volume, extracellular volume and total body water. Although ethanol causes an initial increase in magnesium excretion the possible mechanism(s) have not been investigated. Therefore, renal filtration and tubular transport maximum for magnesium will be determined by the clearance techniques. The effect of ethanol on fecal loss of magnesium which is 60-70% of dietary intake, has not been reported. Another objective of this grant is to determine total magnesium balance (intake-urine and fecal loss) during and after ethanol intake. Finally we have found sodium retention and subsequent extracellular volume expansion to be characteristics of the descending phase and to occur during chronic ingestion. Previous reports suggest that after a single dose, both the set-point and responsiveness of the regulatory systems controlling volume and osmolality are markedly altered by ethanol. Thus, the regulation of the extracellular fluid compartment will be systematically investigated after both acute and chronic ethanol intake. The systems will be challenged by isotonic and hypotonic infusions to ascertain the true set-point for the system and to observe the renal response to the challenge.